Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components.

BACKGROUND: Platelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. STUDY DESIGN: An open label, sequential cohort study of transfusion-dependent hematology-oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment-emergent assisted mechanical ventilation (TEAMV) by non-inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri-transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. RESULTS: By modified intent-to-treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non-inferior to CPC for TEAMV (treatment difference -1.7%, 95% CI: (-3.3% to -0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC. DISCUSSION: PRPC demonstrated reduced TEAMV with no excess treatment-related pulmonary morbidity.

An economic and disease transmission model of human papillomavirus and oropharyngeal cancer in Texas.

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC in Texas. Parameters for the Year 2010 were used as the initial values, and the prediction for Year 2012 was compared with the real age-specific incidence rates in 23 age groups for model validation. The validated model was applied to predict 100-year age-adjusted incidence rates. The public health benefits of HPV vaccine uptake were evaluated by computer simulation. Compared with current vaccination program, increasing vaccine uptake rates by 50% would decrease the cumulative cases by 4403, within 100 years. The incremental cost-effectiveness ratio of this strategy was $94,518 per quality-adjusted life year (QALY) gained. Increasing the vaccine uptake rate by 50% can: (i) reduce the incidence rates of OPC among both males and females; (ii) improve the quality-adjusted life years for both males and females; (iii) be cost-effective and has the potential to provide tremendous public health benefits in Texas.

Cost of treating recurrent respiratory papillomavirus in commercially insured and medicaid patients.

OBJECTIVES: The study objective was to estimate the first 2 years' direct costs of treating new cases of juvenile-onset and adult-onset recurrent respiratory papillomatosis (RRP) and determine the predictors of treatment costs. METHODS: Cases were patients diagnosed with RRP in commercial insurance claims in 2011-2014 and Texas Medicaid in 2008-2012 for treatment of RRP. Controls were patients without a diagnosis of HPV-related cancer or RRP, matched with cases by age, sex, geographic area, date of diagnosis of RRP, and propensity score. Total health care costs in the first 2 years after diagnosis were obtained from cases and matched controls. A generalized linear model was created to identify predictors of monthly costs. RESULTS: In commercially insured patients, a total of 122 cases of juvenile-onset (<18 years old) and 1824 cases of adult-onset (≥18 years old) RRP were identified. The mean first 2 years' cost difference between cases and controls was $58,733 for juvenile-onset disease and $11,185 for adult-onset disease after model adjustments. In the Texas Medicaid population, 73 cases of juvenile-onset and 96 cases of adult-onset RRP were identified. The mean first 2 years' cost difference between cases and controls was $76,115 for juvenile-onset disease and $4,633 for adult-onset disease after model adjustments. CONCLUSION: The first 2 years' medical costs difference of juvenile-onset and adult-onset RRP among commercially insured and Medicaid population were approximately $60,000 to $70,000 and $5,000 to $11,000, respectively, and should be considered in HPV vaccination promotion investment decisions. LEVEL OF EVIDENCE: N/A Laryngoscope, 130:1186-1194, 2020.

Potential Influence on Clinical Trials of Long-Term Survivors of Stage IV Non-small cell Lung Cancer.

BACKGROUND: New, effective treatments have resulted in long-term survival for small subgroups of metastatic non-small cell lung cancer (NSCLC) patients. However, knowledge of long-term survivor frequency and characteristics prior to modern therapies is lacking. METHODS: Surveillance Epidemiology and End Results (SEER) patients with stage IV NSCLC diagnosed from 1991 to 2007 and followed through 2012 were dichotomized by survival time into the 10% who lived 21 months or longer (long-term survivors) vs the remaining 90% and compared with participants in a representative clinical trial of molecular profiling and targeted therapies (CUSTOM). RESULTS: Among the 44 387 SEER patients, the 10% identified as long-term survivors were distinguishable from the remaining 90% by younger age, female sex, Asian race, adenocarcinoma histology, tumor grade, tumor site, and surgery. From 1991-1994 to 2003-2007, median survival increased by 6 months from 30 to 36 months among long-term survivors but by only 1 month from 3 to 4 months among the remaining 90%. Among the 165 participants in the CUSTOM trial, 54% met our SEER criterion of long-term survival by living for 21 months or longer. CONCLUSIONS: Among SEER patients with stage IV NSCLC, long-term survivors had a median survival approximately 10 times that of the remaining 90%. Long-term survivors accounted for more than one-half of the participants in a representative clinical trial. Caution is required when extrapolating the outcomes of participants in clinical trials to patients in routine clinical practice.

Lifestyle behavior patterns and mortality among adults in the NHANES 1988-1994 population: A latent profile analysis.

Evidence suggests interdependent associations of individual modifiable behaviors with health outcomes. However, such interrelations have not been accounted for in previous behavior-outcome associations. We conducted latent profile analysis (LPA) on self-reported levels of alcohol consumption, restaurant dining, vitamin/mineral supplement use, physical activity (PA) and smoke exposure (first- and second-hand smoke) separately for smokers (N = 4530) and non-smokers (N = 13,421) using data from the third National Health and Nutrition Examination Survey (NHANES III) to identify subgroups with similar levels within and across behaviors. Cox-proportional hazards models were used to compare mortality rates between subgroups from cancer, cardiovascular disease (CVD) and all-causes at an average of 16.4 (±6.1) years follow-up. Five behavioral typologies were identified in non-smokers ("Moderates", "Low Risk Factors", "Restaurant Diners", "Moderate Passive Smokers" and "Heavy Passive Smokers"), and four in smokers ("Moderates", "Low Risk Factors", "Heavy Smokers" and "Physically Active"). As a group, "Moderates" had levels of each behavior that were not significantly different from at least one other group. Compared to "Moderates", in non-smokers "Restaurant Diners" had lower hazard from all-cause (hazard ratio (HR):0.84, 95% CI:0.74-0.97) and CVD (HR:0.59, 0.43-0.82) mortality, while "Low Risk Factors" had higher cancer mortality (HR:1.38,1.03-1.84). In smokers, compared to "Moderates", higher hazards for mortality were found for "Heavy Smokers" (all cause: HR:1.34, 1.12-1.60; CVD: HR:1.52, 1.04-2.23; cancer: HR:1.41 1.02-1.96) and "Low Risk Factors" (all-cause: HR:1.58, 1.14-2.17). Taken together, when restaurant dining, PA and smoking exposures are grouped together, novel predictions for mortality occur, suggesting data on multiple behaviors may be informative for risk stratification.

Health Care Costs of Anal Cancer in a Commercially Insured Population in the United States.

BACKGROUND: The incidence and death rate of anal cancer in the United States has been increasing on average 2%-3% per year over the past 10 years. Human papillomavirus (HPV) vaccination is a potentially viable prevention strategy, since about 80% of anal cancers are attributable to HPV. To understand the effect of HPV vaccination, it is important to estimate the treatment costs for the HPV-related disease. OBJECTIVE: To estimate the 2-year per patient mean direct health care costs associated with anal cancer in a commercially insured population in the United States. METHODS: All newly diagnosed anal cancer patients were identified from a 2011-2014 Truven MarketScan database. Matched population controls were selected from the database with a 2-step matching method using demographic, comorbidity, and health care cost variables. Costs for the first 2 years were measured for cancer patients and controls. The difference in costs between the groups was calculated to estimate the costs associated with anal cancer treatment. A generalized linear model with gamma distribution and log link function was applied to estimate the costs for censored months for the patients who did not have at least 2 years of follow-up. RESULTS: 1,976 patients with anal cancer and 1,976 controls were included in the study. The first 2-year per patient adjusted mean cost associated with anal cancer treatment was $127,531 (SD = $189,064). Male sex, cancer diagnosis, higher Charlson Comorbidity Index score, and higher prediagnosis costs were significantly associated with higher monthly costs. Higher psychiatric diagnostic group scores were associated with lower monthly costs. Anal cancer treatment costs were highest in the first 6 months after diagnosis (per patient per month [PPPM] mean = $12,846), leveling off at a much lower monthly cost during the subsequent 18 months of the 2-year period (PPPM mean = $3,717). CONCLUSIONS: The first 2-year costs associated with anal cancer treatment were substantial. Given that approximately 80% of anal cancers are attributable to HPV infection, this study provides important parameters for estimating the potential economic benefit of HPV vaccination. DISCLOSURES: This research was accomplished within the Oropharynx Program at The University of Texas MD Anderson Cancer Center and was funded in part through the Stiefel Oropharyngeal Research Fund. The authors report funding contributions from the Christopher and Susan Damico Chair in Viral Associated Malignancies (The University of Texas MD Anderson). This work was supported by generous philanthropic contributions, including a contribution from the Lyda Hill Foundation, to The University of Texas MD Anderson HPV-Related Cancers Moon Shot Program. The authors have nothing to disclose.

Age-Structured Population Modeling of HPV-related Cervical Cancer in Texas and US.

Human papillomavirus (HPV)-related cervical cancer is a major public health threat to women, with >10,000 new cases diagnosed annually in the United States between 2008 and 2012. Since HPV vaccines can protect against ~80% of HPV-associated cervical cancers, the economic and epidemiological impacts of HPV vaccination have been extensively investigated, particularly at the national level. However, vaccination policies are state-specific, and state-level models are required for state-specific policy decisions. This study adapted an age-structured population model to describe the dynamics of HPV-related cervical cancer in Texas, with model parameters calibrated for Texas. The Year 2000 parameter set was the start point, and the model's predictions from 2001-2010 were well matched with the real incidence numbers in 23 age groups, suggesting the validity of the model. Application of the model to the Year 2010 parameter set predicted that, over the next 10 decades, incidence would decrease rapidly within the first decade and more slowly thereafter. Sensitivity analysis determined the impact of selected parameters (e.g., vaccine coverage rate) on future disease incidence. When compared with the US parameter sets, the Texas population was more sensitive to changes in HPV transmission and vaccination (e.g., ~8% difference in the predicted disease decline).

Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic.

OBJECTIVE: Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are preventive against cardiovascular disease (CVD) and several cancer types, but long-term use has been associated with significant health risks, resulting in conflicting recommendations on NSAID use for prevention of CVD and cancer. Previous research indicates that aspirin use increases with age and CVD risk factors and that a large percentage of the US population regularly use analgesics, including NSAIDs, but there has not been a recent, in-depth assessment of NSAID use prevalence, changes in use over time or predictors of NSAID use in the USA. METHODS: We used the cross-sectional, National Health And Nutrition Examination Survey (NHANES) from 1988 to 1994 and three continuous cycles (1999-2004) to assess regular NSAID use prevalence, changes over time and predictors of regular NSAID use. RESULTS: Overall, regular NSAID use increased over time and varied by demographic features. Participants over 60 years of age, women, participants with high body mass index, increased waist circumference or heart disease were significantly more likely to be regular NSAID users. By contrast, non-Hispanic African American and Mexican American participants were significantly less likely to regularly use NSAIDs. CONCLUSIONS: This study uses a nationally representative data set (NHANES) to provide an exploration of regular NSAID use patterns over time, highlighting several demographic, lifestyle and clinical conditions associated with regular NSAID use. Understanding who is likely to regularly use NSAIDs enables more targeted messaging both for increasing the preventive benefits and for limiting the toxicities associated with regular use of NSAIDs.

Retaining Faculty in Academic Medicine: The Impact of Career Development Programs for Women.

BACKGROUND: For more than two decades, national career development programs (CDPs) have addressed underrepresentation of women faculty in academic medicine through career and leadership curricula. We evaluated CDP participation impact on retention. METHODS: We used Association of American Medical Colleges data to compare 3268 women attending CDPs from 1988 to 2008 with 17,834 women and 40,319 men nonparticipant faculty similar to CDP participants in degree, academic rank, first year of appointment in rank, and home institution. Measuring from first year in rank to departure from last position held or December 2009 (study end date), we used Kaplan-Meier curves; Cox survival analysis adjusted for age, degree, tenure, and department; and 10-year rates to compare retention. RESULTS: CDP participants were significantly less likely to leave academic medicine than their peers for up to 8 years after appointment as Assistant and Associate Professors. Full Professor participants were significantly less likely to leave than non-CDP women. Men left less often than non-CDP women at every rank. Participants attending more than one CDP left less often than those attending one, but results varied by rank. Patterns of switching institutions after 10 years varied by rank; CDP participants switched significantly less often than men at Assistant and Associate Professor levels and significantly less often than non-CDP women among Assistant Professors. Full Professors switched at equal rates. CONCLUSION: National CDPs appear to offer retention advantage to women faculty, with implications for faculty performance and capacity building within academic medicine. Intervals of retention advantage for CDP participants suggest vulnerable periods for intervention.

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSS-induced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage. CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation.